PB1821: THE INFLUENCE OF BCL2, BAX, BAX/BCL2 RATIO AND MDR1 GENE EXPRESSION ON PROGNOSIS OF ADULT DE NOVO ACUTE MYELOID LEUKEMIA PATIENTS WITH NORMAL KARYOTYPE
Authors: Zlatko Pravdic, Nada Suvajdzic, Sonja Pavlović, Mirjana Mitrovic, Marijana Virijevic, Vladimir Gašić, Nikica Sabljic, Nikola Pantic, Irena Marjanovic, Teodora Karan-Djurasevic, Ljubomir Jakovic, Ana Vidovic, Nataša Tošić
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Deregulation of the apoptotic process underlies the pathogenesis of many cancers, including leukemia, but is also important for the success rate of chemotherapy. Therefore, the gene expression profile of main apoptotic factors, such as anti-apoptotic BCL2 (B-cell lymphoma protein 2) and pro-apoptotic BAX (BCL2-associated X), as well as genes involved in the multi-drug resistance (MDR1), could have significant impact on the prognosis of acute myeloid leukemia (AML). Aims: The influence of BCL2, BAX, and MDR1 expression on prognosis in AML patients with normal karyotype (AML-NK). Methods: We analyzed the expression of BCL2, BAX, and MDR1 in bone-marrow samples collected at diagnosis from 51 adult patients (age 18-65 years), male/female (26/25) with de novo AML-NK using real-time polymerase chain reaction method (PCR), and examined their prognostic potential. Baseline detection of FLT3-ITD and NPM1 mutations were analyzed also by PCR. All patients received induction chemotherapy with daunorubicin and cytarabine (3 + 7) followed by three consolidation cycles of high/intermediate doses of cytarabine. Median gene expression values were as follows: BCL2 1.22 (range 0.13-8.97), BAX 0.92 (range 0.27-2.64), BAX/BCL2 ratio 0.62 (range: 0.11-7.77), MDR1 0.16 (range 0.00-13.74). Based on the median expression values, patients were divided into: higher than median (BCL2+, BAX+, BAX/BCL2high and MDR1+) and lower than median (BCL2-, BAX-, BAX/BCL2low and MDR1-) expression groups. Overall and disease-free survival (OS and DFS) were calculated, while patients undergoing hematopoietic stem cell transplantation were censored at the time of transplantation (15 patients). Standard statistical methods were performed. Results: Increased expression of BCL2 (BCL2+) was associated with chemoresistance (p=0.018), while patients with low BAX expression (BAX-) were more prone to relapse (p=0.034). Analysis of the combined effect of BCL2 and BAX expression showed that 87% of patients with BAX/BCL2low ratio were refractory to chemotherapy (p=0.024). High expression of MDR1 (MDR1+) was associated with BCL2+ status (p<0.001), and with absence of NPM1 and FLT3-ITD mutations (p=0.048 and p=0.010, respectively). None of the analyzed genes influenced OS and DFS. Summary/Conclusion: Our analysis of BCL2, BAX and MDR1 gene expression profiles is the first study focusing exclusively on AML-NK patients. Preliminary results showed that patients with high BCL2 expression are likely to be chemo resistant, and possibly may benefit from specific anti-BCL2 treatment. Further investigations conducted on a larger number of patients could elucidate actual prognostic significance of these genes in AML-NK patients. Keywords: AML, ABC transporter, BCL2, Bax